Animal models for AIDS are needed to study the pathogenesis of disease and to facilitate the development of vaccines and drug therapies. Simian Immunodeficiency Virus (SIV) infection of macaques promises to be a valuable system for such studies. SIV is similar to the human AIDS virus HIV in its biological properties, it is related in sequence to HIV and it induces a disease in monkeys with remarkable parallels to AIDS in man. Results of experiments regarding SIV disease pathogensis and vaccine development could suggest reasonable approaches for human AIDS prevention. In the proposed research, molecular determinants of SIV persistence in vivo will be identified and mechanisms by which the persistent virus carrier state is achieved and maintained will be examined. These goals will be achieved through in vitro and in vivo testing of SIV mutants of defined sequence and through analysis of some of the characteristics of persistent SIV infection. The role of defined mutations on tropism and pathogenicity will be examined. Ongoing attempts to achieve protective immunity through vaccination will be extended.